Effect of total flavones of hawthorn leafonon expression of COX-2/Nrf2 in liver of rats with nonalcoholic steatohepatitis / 中国中药杂志

ABSTRACT

To explore the effect of total flavones from hawthorn leaf on (THFL) on the expression of COX-2/Nrf2 in the liver tissues of rats with nonalcoholic steatohepatitis (NASH), and discuss its anti-NASH mechanism, thirty-two SD rats were randomly divided into the normal group, model group, THFL high dose group and low dose group, 8 in each group. High fat diet was given to the rats for 12 weeks to establish the NASH models, and the high and low dose groups were administered with TFHL at the dosage of 250, 125 mg•kg⁻¹•d⁻¹ respectively. Steatosis and the inflammatory changes of the liver tissues in rats were observed by HE staining; T-AOC level was detected by colorimetry; the level of 8-OHdG and the protein expressions of COX-2, Nrf2 and HO-1 in the liver tissues were determined by immunohistochemistry; and the mRNA expressions of COX-2, Nrf2 and HO-1 in liver tissues were detected by Real time-PCR. Compared with the normal group, the liver steatosis, ballooning degeneration for inflammatory degree and NAFLD activity scores (NAS) were significantly increased in model group, while total antioxidant capacity (T-AOC) was decreased, DNA damage marker 8-OHdG level was increased, and the mRNA and protein expressions of COX-2, Nrf2 and HO-1 were significantly increased. After the administration of high and low dose of TFHL, the inflammation degree of the liver tissues and NAS were significantly decreased, 8-OHdG level and COX-2mRNA and protein expressions were decreased, and the mRNA and protein expressions of Nrf2 and HO-1 were significantly increased when compared with the model group. COX-2/Nrf2 pathway was involved in the development and progression of NASH induced by high fat diet. TFHL could prevent the development of NASH by promoting the expression Nrf2/HO-1, regulating and inhibiting the over expression of COX-2, and further attenuating the cell injury and hepatic inflammation caused by oxidation reaction.